PROJECT SUMMARY Through the combined study of individual variation in genes, environment, and lifestyle, precision medicine research offers the potential for discoveries that will improve human health. Spurred by the declining cost of next-generation sequencing, widespread use of electronic health records, proliferation of wearable devices, and other technological advances, the immense scale required for such research is now within reach. These same characteristics, however, escalate the challenge of protecting research participants. Compared to multi- site clinical trials, multi-site precision medicine research differs in fundamental ways, including the use of broad consent to unspecified future use of biospecimens and data; long-term duration; the volume, diversity, and complexity of data amassed; and the evolving nature of the informational risks. Such research implicates state laws that govern an array of topics?such as human subjects research, genetic testing, and both general and genetic privacy and discrimination?which, in turn, can have a significant impact on research practices, including consent disclosures, confidentiality considerations, and offering individual research results to participants, to name just a few. Thus, the choice of which state?s laws apply, and under what circumstances, can substantially alter participant rights and protections in precision medicine research. Traditionally, ?choice of law? questions are addressed in advance through contractual agreement, but that avenue is not available in the ethical conduct of research. Federal law establishes minimum standards for protecting research participants, but many states have enacted additional requirements that are not preempted by federal law and may directly conflict with other states? laws. Because multi-site trials have typically relied on local IRB review and oversight, the problem of accounting for and reconciling state laws has received relatively little attention. However, the nature and scale of precision medicine research, coupled with the new federal requirements for single-IRB review, are likely to bring choice of law issues to rapid prominence. Our objectives for this application are to begin exploring stakeholders? experiences and opinions regarding choice of law questions in the research context, as well as whether and how existing choice of law frameworks might be applied in resolving them. Specifically, we will (1) explore selected stakeholders? experiences and perspectives concerning choice of law questions in multi-site research; and (2) convene a group of renowned legal and research experts to begin evaluating the application of existing choice of law frameworks to multi-site precision medicine research.